Cantharidic anhydride (cantharidin, hydroxyl cantharidin) is an extremely poisonous substance extracted from the body of cantharis, cantharid and the like used in Chinese traditional medicine. Cantharis used as a drug was recorded to have anticancer effect in Chinese traditional medicine long ago. Classical cantharis plaster abroad is a blister formed by combining cantharis powder with bee wax, rosin, tallow etc. In the said plaster, the content of cantharis powder was 25%. According to solubility calculation and test observation, most of the cantharidic anhydride was not dissolved in the course of plaster preparation. Therefore this classical skin-irritating agent was only a manufactured product of cantharis powder. In recent years, especially after the discovery of that cantharidic anhydride can serve as anticancer drugs, studies on the pharmacology and clinical application of cantharidic anhydride grows rapidly. At present, cantharidic anhydride is obtained by the extraction of cantharis powder by organic solvents such as acetone, chloroform, ether and the like. In order to improve the yield of cantharidic anhydride from the conversion of magnesium cantharidate, people usually treated cantharis powder with concentrated hydrochloric acid before the extraction of cantharidic anhydride with organic solvents. The obtained cantharidic anhydride or hydroxyl cantharidic acid were then purified and made into pharmaceutical composition, for example, cantharidin tablet (Shanghai Q/WS-1-566-80) and cantharidin injection (Shanghai Q/WS-1-567-80) have been granted.
Recently it was found that cantharidic anhydride is an antiviral antibiotics. However, in human body and animal body, the said antibiotic effect of cantharidic anhydride is not obvious for non-fat-soluble species but is quite well for fat-soluble cantharidic anhydride (Journal of Nature, 1980, Vol. 3, 458 in Chinese), especially in the case of treating viral hepatitis. Preparations made from fat-soluble cantharidic anhydride are specific for such diseases. The present inventor has already disclosed the preparation of cantharidic anhydride in his early Chinese Patent Application (ZL 90106365.7). The preparation for the fat-soluble cantharidic anhydride pharmaceutical composition mainly comprises the following steps:                1. Firstly cantharis powder was soaked in organic solvents such as acetone, dichloromethane, trichloromethane and ether to extract the cantharidic oil and cantharidic anhydride in the cantharis powder into the organic phase.        2. After the cantharis powder was extracted with organic solvent, the residue was dried and then was soaked in solution of concentrate hydrochloric acid and acetone. Cantharidic acid is converted into cantharidic anhydride by concentrated hydrochloric acid and cantharidic anhydride is dissolved into organic phase by using acetone.        3. After the cantharidic anhydride and cantharidic oil in the above-mentioned organic phase were separated from the organic phase, petroleum ether was added to extract the cantharidic oil and thus the separation of cantharidic anhydride from cantharidic oil was achieved. The cantharidic anhydride obtained was combined with that separated in step 2.        4. A definite amount of cantharidic oil was added to refined fat and then a amount of cantharidic anhydride was added and the mixture was stirred and heated at 80-120° C. and finally intermediate product of fat soluble cantharidic anhydride was obtained.        
The above-mentioned refined fat can be vegetable oils such as soy bean oil, corn oil vegetable seed oil, sun flower seed oil, sesame oil, cocoa butter and etc, or wool fat, tallow and the like.
The drugs containing fat solvent of cantharidic anhydride in the above-mentioned patent having good application value. However, the kind of formulation is limited by the nature of fat solvent and drug. For example, the preparatory technology and clinical operation of the injection made of fat solvent are not satisfied and convenient.
On the other hand, one third of the effective components of cantharidic anhydride in the body of cantharis exists in the form of salt of cantharidic acid. Therefore, in traditional Chinese medicine, the effect of medicine also comprises that from magnesium cantharidate when cantharis body was used as oral medication. Since salt of cantharidic acid is easily soluble in water, it would have advantage in preparatory technology and clinical operation. The method of extraction of magnesium cantharidate or salt of cantharidic acid from the body of cantharis and convertion them into purified product are quite complex and have a low yield. It is much more simple, economic, convenient to purify cantharidic anhydride first and then prepare pure salt of cantharidic acid through semi-synthesis. The existence of magnesium cantharidate and salt of cantharidic acid in natural cantharis body indicates that they exhibit biological antibiotic effect in the living cantharis body. Compared with cantharidic anhydride, they have the advantage of higher solubility in the body fluid of cantharis. Therefore salt of cantharidic acid has its own character to be an antibacterial and antiviral drug.
In addition, antiviral preparations containing salt of cantharidic acid are convenient to use, have antibiotic effect to many kinds of important bacteria and viruses and have applicability to wide range of medical practices. Several kinds of pharmaceutical preparations made of salt of cantharidic acid have similar antiviral effect as fat solvent-cantharidic anhydride. Pharmaceutical preparations made of salt of cantharidic acid can be used to certain fields of medical treatment and disease prevention that fat solvent-cantharidic anhydride can not be used.
The above-mentioned technology was disclosed in detail in another patent (ZL931101573) of the present inventor. However the preparatory technology for pharmaceutical preparations of salt of cantharidic acid is more complex and thus the manufacturing cost is higher.
Besides, as mentioned above, although cantharidic anhydride has antiviral effect, there is not any report regarding antibacterial effect for bacteria such as tubercule bacillus.